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PARKIN, PINK1, and DJ1 analysis in early-onset Parkinson’s disease in Ireland

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Abstract

Background

Variants in PARKIN, PINK1, and DJ1 are associated with early-onset Parkinson’ disease (EOPD, age-at-onset < 45). We previously reported a single PINK1 and a single DJ1 heterozygous variant carrier.

Purpose

We aimed to expand upon our previous EOPD studies and investigate for any genotype–phenotype correlations in Irish PD.

Methods

Three hundred fourteen PD patients were recruited from Dublin Neurological Institute, Ireland. Genetic analysis was performed at the Mayo Clinic, Jacksonville, USA. We screened 81 patients with young-onset PD (age-at-onset < 50), of which 58 had EOPD.

Results

We identified 4 patients with homozygous/compound heterozygous variants and 3 heterozygote carriers (pathogenic PINK1/DJ1 variants were not found). Expansion of one of the pedigrees showed a novel variant in exon 9, in a symptomatic patient. We identified 6.89% PARKIN variant carriers associated with EOPD.

Conclusion

These findings suggest that PINK1 and DJ1 are rarely associated with Irish YOPD, while PARKIN variant frequency is similar to that reported worldwide.

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Fig. 1

Data Availability

The data will be provided upon a reasonable request.

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Acknowledgements

The authors would like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies which produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926), and the Heart GO Sequencing Project (HL-103010).

Mayo Clinic is an American Parkinson Disease Association (APDA) Mayo Clinic Information and Referral Center, an APDA Center for Advanced Research and the Mayo Clinic Lewy Body Dementia Association (LBDA) Research Center of Excellence.

Funding

OAR is supported by the National Institutes of Health (NIH; R01 NS78086; U54 NS100693; U54 NS110435), the US Department of Defense (W81XWH-17–1-0249), The Little Family Foundation, the Mayo Clinic Center for Individualized Medicine, and the Michael J. Fox Foundation. TL is supported by Health Research Board and Michael J. Fox Foundation. All the other authors have nothing to declare.

Author information

Author notes

  1. Diana A. Olszewska, Allan McCarthy, Owen A. Ross, and Tim Lynch contributed equally to this work.

Authors and Affiliations

  1. The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland

    Diana A. Olszewska, Allan McCarthy & Tim Lynch

  2. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA

    Diana A. Olszewska, Alexandra I. Soto-Beasley, Ronald L. Walton & Owen A. Ross

  3. Health Affairs & School of Medicine and Medical Science, University College Dublin, Dublin, Ireland

    Diana A. Olszewska, Owen A. Ross & Tim Lynch

  4. Department of Neurology, The Adelaide and Meath Hospital, Dublin, Ireland

    Allan McCarthy

  5. Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA

    Owen A. Ross

Authors
  1. Diana A. Olszewska
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  2. Allan McCarthy
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  4. Ronald L. Walton
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  5. Owen A. Ross
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  6. Tim Lynch
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Contributions

DAO: study idea and design, study recruitment and phenotypic assessment, DNA extraction, laboratory work, interpretation of the results and statistical analysis, preparation of the first draft of manuscript, correction, and approval of the final draft. AMcC: study idea and design, study recruitment and phenotypic assessment, DNA extraction, laboratory work, interpretation of the results, preparation of the first draft of manuscript, critique, and approval of the final draft. AISB: laboratory work, critique, and approval of the final draft. RLW: laboratory work, critique, and approval of the final draft. OAR: study idea and design, lead of the laboratory work and expertize, overlooking the laboratory work at the Mayo Clinic, expertize in the interpretation of the results, critique, and approval of the final draft. TL: study idea and design, lead of the neurological expertize, overlooking the study in the Dublin Neurological Institute, critique, and approval of the final draft.

Corresponding author

Correspondence to Diana A. Olszewska.

Ethics declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Mater Misericordiae University Hospital, Dublin, Ireland, ethical approval number 1/378/1300) and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards.

Consent to participate/publication

Informed, written consent was obtained from all the patients included in the study.

Conflict of interest

The authors have no competing interests.

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Olszewska, D.A., McCarthy, A., Soto-Beasley, A.I. et al. PARKIN, PINK1, and DJ1 analysis in early-onset Parkinson’s disease in Ireland. Ir J Med Sci 191, 901–907 (2022). https://doi.org/10.1007/s11845-021-02563-w

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  • DOI: https://doi.org/10.1007/s11845-021-02563-w

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